Week 7 - Understanding the Resting Membrane Potential
Law of Macroscopic Electroneutralilty: overall, an ion solution is electrically neutral
extracellular fluid and the cytosol have the same number of + and - charges
even though the thin layers differ, the overall charge is neutral
thin layer on the edge of the cytosol is negative
thin layer on the extracellular membrane is positive
ex. if the entire class is a 50:50 ratio of males to females, it does not necessarily mean each row has a 50:50 ratio of males to females
Volt is a unit of electrical potential difference
Voltmeter is used to measure the difference between voltages
by convention, resting membrane potential is measured as “inside” compared to “outside” to minimize confusion
if the voltmeter reads -70mV, that means the recording electrode (on the thin layer of the cytosol) is -70mV compared to the reference electrode (on the thin layer of the extracellular fluid)
intracellular recording
Extracellular recording is when the reference electrode and recording microelectrode are both on the extracellular layer, but they see changes in charge when the extracellular environment changes
voltage difference will occur when ions are moving in and out
measurement over time
All cells are polarized
have a resting membrane potential
not only neurons
but the value differs among different cell types
neurons have a resting membrane potential to communicate information
Free energy is inversely proportional to the electrical potential difference
free energy is the energy available for work and biosynthesis
ex. the energy used to move an ion from one place to another, to circulate blood, etc.
resting membrane potential is an example of electrical potential difference
the closer the electrical potential difference is to 0 (small magnitude), the greater the release of free energy
free energy must be used (so starts to decrease) as the resting membrane potential increases
because it takes energy to pump ions against the concentration gradient to reach equilibrium
Sodium-Glucose Transporter:
protein that brings glucose into a cell
even when the concentration of glucose is higher inside the cell than outside
against the concentration gradient
when Na+ comes in, the inside becomes more positive, which decreases the magnitude of the membrane potential (originally it is more negatives, so adding positive ions makes it more neutralized)
according to the free energy equation, if the membrane potential decreases, then more free energy is released
this free energy is used to power glucose to come in, against the concentration gradient
therefore, not all cellular work and biosynthesis is directly linked to ATP
in this case, the source is membrane potential
Resting Membrane Potential is established because the ion concentrations inside and outside differ
extracellular is dominated by Na+ and Cl-
cytosol is dominated by K+, PO43- and Pr (proteins)
proteins usually carry a -ve charge
Equilibirum Potential
the value of membrane potential at which the net flux of ion across the membrane is zero
two gradients (electrical and concentration) are balanced
measured using the Nernst Equation, dependent on concentration, charge, and concentrations
as temperature increases, the magnitude of membrane potential also increases
increased temperatures cause molecules to move easily
if they move more, a bigger electrical gradient is required to oppose it
K+:
resting membrane potential arises because of the ion gradient
concentration gradient will move the ions from inside to outside
eventually, the inside will become more negative, which will start to move the ions back inside with the electrical gradient
higher concentration inside than outside
if the equilibrium potential value is -89mV, then it means that K+ will leave until the inside becomes -89mV, which is when the electrical gradient will start pulling it back in at the same rate
but this movement is very small compared the the large amount of ions in a cell, so the difference is negligible
not violating the Law, as the law is simply an approximation
If the membrane potential is not equal to the equilibrium potential, then net movement of ion across the membrane will occur
if the membrane potential is -100mV, and the equilibrium potential is -89mV, then K+ must be pushed back in until it reaches -89mV to be at equilibrium
Na+:
resting membrane potential arises because of the ion gradient
concentration gradient will move the ions from outside to inside
eventually, the inside will become more positive, which will start to move the ions back outside with the electrical gradient
higher concentration outside than inside
ex. +72mV
the value that the membrane potential is trying to reach for sodium
Cl-:
resting membrane potential arises because of the ion gradient
concentration gradient will move the ions from outside to inside
eventually, the inside will become more negative, which will start to move the ions back outside with the electrical gradient
ex. -84mV
the value that the membrane potential is trying to reach so that the net flux of Cl- is 0
Normally, cell membranes are impermeable to charged species
hydrophobic core
so these ions move through protein leak channels
always open
K+ leak channels are more abundant because the relative ion permeability of K+ is 100, when Cl- is 10, and Na+ is 1
Roommate Analogy:
when a man and a woman are roommates, woman prefer 85 degrees Fahrenheit where men prefer 65
just like how Na+ and K+ prefer different equilibrium potentials
if rent is 50/50, it is fair that the temperature is set to 75, an even split in the middle
but if the man pays more rent, the temperature should be set to a value close to the man’s preference
but if the woman pays more, the temperature should be set to a value close to her preference
it depends on who contributes more to the cost
At rest, neither Na+, K+ or Cl- are at equilibrium
resting membrane potential is a steady state
Goldman Equation:
determines the resting membrane potential based on all ions depending on how much they contribute (permeability)
if the value is -85mV, that is closer to the equilibrium value of K+ because it has the highest permeability
Week 7 - Lab
Intracellular action potentials:
intracellular action potential recordings allow us to examine the behaviour of a single excitable cell (like neurons or muscle fibers)
but these are difficult to do
Extracellular action potentials:
from single cells are possible but only when the cell is large and isolated from other cells (like earthworm nerve cord)
In most multicellular animals, multiple neurons are found in close association
most nerves in our bodies are composed of dozens or hundreds of axons each
Compound action potential
like a single action potential, there is a minimum threshold stimulation intensity below which no CAP will be elicited
unlike a single action potential the amplitude of the CAP can change as stimulation intentisty is increased
CAP is made up of the roughly synchronous firing of multiple axons within the nerve
Conduction velocity:
may differ per individual action potentials because some axons might be larger in diameter than others
the average conduction velocity of the population of axons can be measured
Refractory period:
following each firing, the neuronal membrane becomes briefly refractory
absolute refractory period → the axon will not fire again even if it is stimulated with a suprathreshold stimulus
relative refractory period → an axon will fire again, but only if it is stimulated with a suprathreshold stimulus and the amplitude of the action potential will be reduced
By delivering multiple stimulation pulses in succession, increasing there stimulation frequency (thus decreasing the delay between stimulation pauses), you will eventually see that a CAP no longer exists for each stimulation pulse.
In summary, increasing the frequency of stimulation pulses reduces the time available for recovery between each pulse.
When this happens, the nerve or muscle fibers can no longer generate individual action potentials, leading to the disappearance or reduction of the CAP.
The rising phase is when a large number of voltage-gated Na+ channels open and allow a net influx of sodium with the concentration gradient
this causes the membrane potential to rise as it becomes more positive
The resting potential begins to fall (repolarization) when:
voltage-gated K+ channels also are triggered at the same time but are slower to respond
offsets the influx of positive current from a new stimulus → leads to a relative refractory period as it contributes to a relative inability of this portion of the membrane to initiate a new action potential
or voltage-gated Na+ channels stop permitting the flow of Na+ as their inactivation gates swing to the closed position
remain in the closed position until the membrane repolarization back below the threshold occurs, and the channels cannot reopen again
this leads to an absolute action potential
Both CAP conduction velocity and duration of the absolute refractory period can be affected by temperature.
Week 8 - Comparative Digestive Physiology
Variation in Food Quality:
quality refers to how easily the food can be digested
animal foods are typically high quality
while plant foods are typically low quality except nectar
refractory refers to resistance to degradation (digestion)
Animal foods contain a lower portion of compounds that are difficult to digest than plant foods
The type of diet is based on quantity vs. quality
plant vegetation is probably the most abundant food source on Earth
cellulose is the most abundant organic compound on Earth
animal diets are high quality but less abundant while plant diets are low quality and more abundant
Type of Diet:
most animals are omnivores
most plants are also omnivores
but the number of pure herbivores is greater than the number of pure herbivores
Evolution:
it is difficult to change from one end of the spectrum to the other end
ex. herbivores to carnivores or carnivores to herbivores
so this is less common
what is most common is the transition of herbivores becoming omnivores
and next most common is carnivores to omnivores
transition to omnivory has become evolutionarily favourable (frequent)
as competition for specialized food resource increases, there is increased pressure to incorporate additional food resources
as the competition for fish in piscivores increases it’ll be more difficult to meet energetic demands so they start eating like an omnivore
population increase or prey number decrease can cause these shifts
Foraging Costs:
generally, the bigger you are, the larger the home range you have to patrol
herbivores: search costs are low and handling costs are low
but even considering body mass, herbivores tend to patrol less range than carnivores because plants are abundant so it is easy to find food
carnivores: search costs are high and handling costs are high
it is harder to hunt animals
ex. chasing
chasing something smaller is easier but the reward is not enough, so the amount of small stuff you must chase is more compared to one big thing to get the same reward
some plants are not as easy to digest
ex. thorns
some plants produce toxins too, so the handling cost is high because the predator must be able to detoxify it
Detoxification Limitation Hypothesis
feeding is limited by the animals capacity to detoxify
bitter taste → toxic
plants have a greater capacity to detect toxins in than diet than carnivores or omnivores
they encounter more toxins
2TR receptors detect bitter compounds so they are more abundant in plants
plant secondary metabolites (PSM) include toxins
if the animal does not eat the plant with PSM, then there is a cost because it found food but can’t eat it
if the animal does eat it, it must be either modified in the gut…
metabolized by microbes (detoxify), inactivated in the gut environment (stomach acidity), or modified by endogenous compounds
…or if it is not modified in the gut
it must be excreted in feces
or absorbed which involves oxidation, hydrolysis, methylation, acetylation, glucuronidation, glycine conjugation, and sulfur conjugation
but these are very costly
generalist herbivores have all the absorbance pathways at low levels
specialist herbivores have one pathway at high levels
focus on one particular plant with specific PSMs
Brushtail possum:
feeds on Eucalyptus
melliodora and radiate
when it is only eating one or the other, it can’t eat more than 25g/kg because its detoxification capacity is low (generalist)
it can eat more when it eats both because each one produces its own PSM, so the generalist has all of the pathways to digest each type at low levels
combined it can have more
Carnivores:
simple gut → because of the high-quality foods that are easy to digest
sac-like stomach + tube-like intestine
Herbivores:
not as simple
contain fermentation chambers that house large numbers of microbes, which digest refractory compounds
ex. cellulose
the location of the chambers can differ
Pandas (herbivores) come from carnivore ancestors so it still has the carnivore-like gut
they only absorb 10% of what they eat
so they are always eating and pooping because they cannot digest but they still need to eat a lot to get enough energy
a domestic donkey with a fermentation chamber digests 40-70% of what it eats
so there is a benefit to having this expensive gut
Cost of Gut Maintenance
for herbivores to maintain a complex gut is it expensive?
Burmese python
eats once a month
small intestine doubles in size after eating a meal → to start digestion
and then tears down
when measuring the difference in SMR between frequent eaters and infrequent eaters, the SMR is 20-30% lower
the maintenance cost of the digestive gut is what drives the 20-30% increase in metabolic rate
gut epithelial cells:
get damaged easily because of foods
need to be replaced often
when there is lots of thymidine present, more cell division is taking place to rebuild new cells
this is what drives the cost of maintaining a gut
Gene eliminations:
NOX1 is lost in carnivores
macrophages express NOX1 because they find pathogens and kill them with superoxide
superoxide is produced when NADPH Oxidase in NOX1 uses NADPH to synthesize superoxide (damaging to molecules)
herbivores use NOX1 to prevent bacteria in their fermentation chamber from spilling out and making the body ill
they kill the bacteria that get away with superoxide produced from NOX1
prevents bacterial overgrowth and spillover
In experimental trials, genes with NOX1 knockouts have increased bacterial growth compared to those with NOX1
Week 8 - Lab
Muscles are comprised of cells known as muscle fibers
Red fibers:
slow oxidative fibers
Type I fibers
produce ATP primarily via oxidative phosphorylation
aerobic pathway
contract and relax slowly because ATP is